Noscapine shows antimalarial activity against Plasmodium falciparum 3D7,its clinical isolate Pf140/SS,and Plasmodium berghei ANKA

Objective:To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain(Pf3D7),its clinical isolate(Pf140/SS),and Plasmodium berghei ANKA(PbA).Methods:Using ring-stage survival assay,phenotypic assessments,and SYBR-green-based fluorescence assay,the antimalarial activities of noscapine were assessed compared with dihydroartemisinin(DHA)in in vivo and in vitro studies.In addition,hemolysis and cytotoxicity tests were carried out to evaluate its safety.RT-PCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease Plasmodium falciparum falcipain-2(PfFP-2).Results:The antimalarial efficacy of noscapine against Pf3D7 and Pf140/SS was comparable to DHA,with IC50 values of(7.68±0.88)and(5.57±0.74)nM/mL,respectively,and>95%inhibition of PbA infected rats.Noscapine also showed a safe profile,as evidenced by low hemolysis and cytotoxicity even at high concentrations.Moreover,PfFP-2 expression was significantly inhibited in both noscapine-treated Pf3D7 and Pf140/SS(P<0.01).Conclusions:Noscapine has antimalarial properties comparable to standard antimalarial DHA with better safety profiles,which may be further explored as a therapeutic candidate for the treatment of malaria.

Dengue and falciparum malaria co-infection in travelers returning from Burkina Faso:Report of two cases in Northeastern Italy

Rationale: Malaria and dengue are the most prevalent vector-borne diseases in tropical countries. Plasmodium parasite and dengue virus(DENV) concurrent infection is possible and often under-recognized in geographical areas where these infections are both endemic.Patients concern and diagnosis: We describe the first two cases of Plasmodium falciparum and DENV-3 co-infection in travelers returning to northeastern Italy from Burkina Faso during 2013-2014.Interventions: Malaria infection in both patients was treated with mefloquine. Due to the persistence of symptoms despite of the antimalaria treatment, dengue was also investigated;the treatment of dengue was symptomatic.Outcomes: The patients were discharged in good general condition.Lessons: The need for surveillance of potential malaria and dengue co-infection in travelers returning to Europe from endemic areas is highlighted, as infection with Plasmodium does not exclude arboviral co-infection.

Association of ABO blood group and Plasmodium falciparum malaria in Dore Bafeno Area,Southern Ethiopia

Objective:To assess the distribution of ABO blood group and their relationship with Plasmodium falciparum(P.falciparum) malaria among febrile outpatients who sought medical attention at Dore Bafeno Health Center,Southern Ethiopia.Methods:A total of 269 febrile outpatients who visited Dore Bafeno Health Center,Southern Ethiopia,were examined for malaria and also tested for ABO blood groups in January 2010.The blood specimens were collected by finger pricking,stained with Geimsa,and examined microscopically.Positive cases of the parasitemia were counted.CareStart^(TM) Malaria PflPv Combo was also used to test the blood specimens for malaria.ABO blood groups were determined by agglutination test using ERYCLONE antisera.Data on socio-demographic characteristics and treatment status of the participants were also collected.Chi-square and ANOVA tests were used to assess the difference between frequencies and means,respectively.Results:Out of a total of 269 participants,178(66.2%) febrile patients were found to be infected with Plasmodium parasites,among which 146(54.3%),28(10.4%),and 4(1.5%) belonged to P.falciparum,P.vivax,and mixed infections,respectively.All febrile patients were also tested for ABO blood groups and 51.3%,23.5%,21.9%and 3.3%were found to be blood types of 0,A,B and AB,respectively.Both total malaria infection and P.falciparum infection showed significant association with blood types(P<0.05).The proportion of A or B but not 0 phenotypes was higher(P<0.05) in individuals with P.falciparum as compared with non-infected individuals.The chance of having P.falciparum infection in patients with blood groups A,B and AB was 2.5,2.5 and 3.3times more than individuals showing blood 0 phenotypes,respectively.The mean P.falciparum malaria parasitemia for blood groups A,B,AB,and 0 were 3 744/μ L,1 805/ μ L,5 331/μ L,and1 515/μ L,respectively(P<0.01).Conclusions:The present findings indicate that individuals of blood groups A,B and AB are more susceptible to P.falciparum infection as compared with individuals of blood group O.Nevertheless,further in depth studies are required to clearly establish the role that ABO blood group plays in P.falciparum malaria.

Implication of Oxidative Stress and Antioxidant Defence Systems in Symptomatic and Asymptomatic Plasmodium falciparum Malaria Infection among Children Aged 1 to 15 Years in the Mount Cameroon Area

It is known that the pathogenicity of Plasmodium induces the breakdown of haemoglobin, which leads to the induction of oxidative stress. This study aimed to identify the possible effects of oxidative stress and antioxidant defence systems in symptomatic and asymptomatic Plasmodium falciparum malaria infection in children (1 - 15 years old) in the Mount Cameroon vicinity. This cross-sectional study involved blood samples collected from 473 children and examined for malaria parasitaemia. Full blood counts were performed using an automated haemoanalyser. Serum oxidative stress status (malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and vitamin C (Vit C)) were each determined by colorimetric enzymatic assays. The prevalence of malaria parasite infection was 32.1% among the participants. Out of that, 62.5% of patients with parasitaemia were symptomatic. Anaemia prevalence increased significantly with parasite density. MDA levels were significantly higher in patients with malaria symptoms than in those without symptoms. A significant and positive correlation was detected between MDA (r = 0.831, P < 0.05), NO (r = 0.779, P < 0.05), and malaria parasite density while, a significant and negative relationship occurred between parasite density and GSH (r = ?0.763, P < 0.05) and Vit C (r = ?0.826, P < 0.05) levels, SOD (r = ?0.621, P < 0.05) and CAT (r = ?0.817, P < 0.05) activities. The SOD activity and GSH level significantly decreased (P < 0.05) with an increase in the MDA levels. These findings showed that MDA and nitric oxide levels increased both in malaria participants with or without symptoms. A similar decrease in the antioxidant defence system was observed in both symptomatic and asymptomatic patients. Therefore, there is a need to develop public health policies that encourage routine diagnosis and treatment of malaria in seemingly healthy people (asymptomatic cases), and this will play an essential role in controlling malaria in tropical countries.

Acquisition of naturally acquired antibody response to Plasmodium falciparum erythrocyte membrane protein 1-DBLα and differential regulation of IgG subclasses in severe and uncomplicated malaria

Objectives: To explore whether individuals infected with Plasmodium falciparum(P. falciparum) develop antibodies directed against Pf EMP1-DBLa, and to assess their IgG subclass distribution in severe and uncomplicated malaria.Methods: The anti-PfDBLα IgG and their IgG subclass distributions in plasma of severe(SM) and uncomplicated malaria(UCM) were assessed by enzyme-linked immunoabsorbent assay. The antibody profiles to P. falciparum blood stage antigens were evaluated. CD36 binding ability was determined by static receptor-binding assays.Rosette formation was performed by staining with acridine orange.Results: Significantly higher number of UCM(86.48%) than SM(57.78%) plasma contained total acquisition of specific IgG to P. falciparum antigens(P = 0.000). Similar manners were seen in response to P. falciparum DBLa with significant difference(UCM,59.46% vs SM, 40.00%; P = 0.014). Anti-PfDBLα-IgG1 and-IgG3 were the predominant subclasses. Similar percentage of UCM(31.82%) and SM(33.33%) plasma contained only IgG1, while 13.64% of UCM and 27.78% of SM plasma contained only IgG3. AntiPfDBLα-IgG1 coexpressed with more than one subclass was noted(UCM, 27.27%; SM,16.67%). Obviously, IgG1 coexpressed with IgG3(9.09%) was observed in only UCM plasma. IgG1 was coexpressed with IgG2 in UCM(9.09%) and SM(11.11%) plasma,while IgG1 was coexpressed with IgG4 only in UCM plasma(4.55%). IgG subclasses to P. falciparum antigens were distributed in a similar manner. Only the levels of IgG1, but not IgG3 were significantly higher in UCM than in SM.Conclusions: These data suggest that individuals infected with P. falciparum can develop the anti-Pf EMP1 antibodies with the major contribution of specific IgG subclasses. The balance and the levels of anti-PfDBLα IgG subclasses play a crucial role in antibody mediated protection against severe malaria.

Sequence Analysis and Genotypes of Glutamate Rich Protein of Plasmodium falciparum Isolates from Different Malaria Endemic Areas in China

Objective To sequence the gene encoding glutamate rich protein (GLURP) andidentify the genotypes of geographically different Plasmodium falciparum (P. f ) isolatesfrom China. Methods The gene of R2 repeat region of GLURP was amplified by nestedpolymerase chain reaction and cloned into T-vector. The nucleotide sequence of GLURPgene was determined by automatic sequencer (Dideoxy termination method) and analyzed byDNA Star software. Results At least 7 different GLURP genotypes ranging from 600 bpto 1 500 bp were found in Yunnan and Hainan provinces. R2 region of GLURP gene consistedof several repeat units. Each repeat unit was composed of 19-20 residues which were shownto be highly conserved. GLURP gene was also size polymorphic due to differences in thenumber of repeat units, whereas the repeat sequence was conserved. Sequence analysisshowed that DNA sequences and deduced amino acid sequences were highly homologousamong the geographically dispersed isolates or various isolates from the same geographicalregion. No obvious differences were found in the GLURP gene sequences amonggeographically different isolates. Conclusion GLURP gene is highly structure conservedand size polymorphic, and so is useful in searching for malaria vaccine candidate antigen anddeveloping a genotyping method for malaria research.

Haemophagocytic lymphohistiocytosis secondary to Plasmodium falciparum malaria: Case report and review of the literature

Rationale:Haemophagocytic lymphohistiocytosis is a rare complication of malaria,which is often misdiagnosed.Patient concerns:A 30-year-old male was admitted to our department for persistent fever,which began after returning from a stay in Guinea-Conakry.The laboratory investigations revealed a pancytopenia and an elevated C-reactive protein.Peripheral smear examination showed Plasmodium falciparum,therefore confirming the diagnosis of malaria.The laboratory tests showed a worsening pancytopenia.Bone marrow aspiration and biopsy revealed images of hemophagocytosis.Diagnosis:The diagnosis of haemophagocytic lymphohistiocytosis complicating malaria infection was established.Interventions:The patient was treated with artemether-lumefantrine.No immunosuppressant treatment was delivered to the patient.He received antipyretic and antimalarial treatment only.Outcomes and lessons:We report a case of haemophagocytic lymphohistiocytosis trigged by malaria infection and we review all reported cases secondary to Plasmodium falciparum malaria by searching PubMed publications till October 2019.Haemophagocytic lymphohistiocytos secondary to malaria should be suspected even in non-severe cases of malaria.

Chalcone analogue as potent anti-malarial compounds against Plasmodium falciparum:Synthesis,biological evaluation,and docking simulation study

To investigate in vitro antimalarial activity of chalcone derivative compounds against Plasmodium falciparum 3D7 (Pf3D7) strain and in silico antimalarial activity.MethodsSynthesis of the chalcone derivatives was conducted via Claisen-Schmidt method using NaOH 60% base as catalyst. An in vitro antimalarial activity assay was carried out according to the Rieckmann method against the chloroquine-sensitive Pf3D7 strain. Molecular docking studies of the prepared compounds were performed using Discovery Studio 3.1 (Accelrys, Inc., San Diego, USA) software to dihydrofolate reductases-thymidylate synthase (PfDHFR-TS) protein with Protein Data Bank ID of 1J3I.pdb (sensitive-protein) and ID: 4DP3.pdb (resistance-protein).ResultsThis work has successfully synthesized seven chalcone derivatives with a great antimalarial activity. It has been revealed that allyloxy, hydroxy and alkoxy functional groups could increase the antimalarial activity of the chalcone derivatives. The best antimalarial activity of the prepared compounds was possessed by 3b with an IC50 value of 0.59 μM and categorized as an excellent antiplasmodial. Molecular docking studies of 3b showed binding interaction with the amino acid residues such as Ala16, Ile164, Phe58, Tyr170 of the 1J3I.pdb protein and also Ala16, Phe58, Ile112, Met55 of the 4DP3.pdb protein.ConclusionsAn in vitro antimalarial assay of the prepared chalcone derivative (3a-g) showed an excellent and good antiplasmodial activity against the chloroquine-sensitive Pf3D7 strain. In silico antimalarial studies revealed that 3a-g made binding interaction with both sensitive-protein (1J3I.pdb) and resistance-protein (4DP3.pdb), which means that they were both active against chloroquine-sensitive and resistant plasmodium strain.

A Comparative Study of Dihydroartemisin in Compounds in Treatment of Uncomplicated Falciparum Malaria in Kampong of Cambodia

Objective: To compare the safety and efficacy of two compounds of dihydroartemisinin(DHA) -Artekin and Artekin (T) in the treatment of uncomplicated falciparum malaria. Methods:The regimen of 8-tablet for 2 days of Artekin and Artekin (T) were applied to 100 patients with uncomplicated falciparum malaria, who were randomly divided into two groups. Each group contained 50 cases. The cure rate, the mean parasites clearance time, the mean fever clearance and side-effects were observed to assess the safety and efficacy of the compounds used. Results: The mean parasites clearance time was 31. 7±9.0 hours in the Artekin group and 32. 8±8. 8 hours in Artekin (T) group respectively; the mean fever clearance time was 12. 7±7. 2 hours in Artekin group and 16. 5±7. 9 hours in Artekin (T) group; there were no recrudescence case in both groups within the 28 days of follow-up, the cure rates in Artekin group and Artekin (T) groups were 100%. It indicated that the tolerability of both compounds were very good, the side-effects such as nausea, abdominal pain were mild and self-limited. Conclusion: The study preliminarily indicated that the DHA and PQ compounds were of high efficacy, rapid acting and low toxici-ty. Artekin is very promising as a cheap, simple, effective treatment for multi-resistance malaria in Cambodia.

Definition of hyperparasitemia in severe falciparum malaria should be updated

Hyperparasitemia is one criterion of severe falciparum malariaby World Health Organization(WHO)for more than two decades[1].Although there is a correlation between density of parasittemiaand severity of malaria,some individuals with high parasite countsmay not be severely ill,whereas others with low parasitemia mayhave ultimately fatal infections.Hyperparasitemia(more than 5%

Investigation of the Efficacy of Home-Based Oral Chloroquine Treatment among Under-Five Children with Plasmodium falciparum Malaria in Some Parts of Jos, Plateau State, Nigeria

Background: Nigeria is currently a malaria endemic country with an estimated 76% of her population at risk of contracting malaria [1]. According to a study in Nigeria, the first line of action mothers took when their children under 5 years have malaria showed that over 50% of them used non-prescription drugs they have at home or bought from pharmacy stores. And 60% of the most commonly used drugs for malaria treatment were chloroquine [2]. Many recent studies have demonstrated re-emergence of chloroquine-sensitive P. falciparum, suggesting a possible role in future malaria control [3]. Objective: The aim of this study was to investigate the effect of home-based oral chloroquine treatment among children under 5 years with Plasmodium falciparum malaria attending Jos University Teaching Hospital and OLA Hospital in Jos Metropolis. Method: This is a cross-sectional study of 93 malaria and non-malaria children. Malaria diagnosis was carried out using microscopical examination of Leishman’s stained thick and thin blood films, P. falciparum parasitemia was assessed by standard microscopy techniques and complete blood count was done using Beckman Coulter Analyzer. Results: The body temperature on admission was significantly lower (p &#730;C ± 0.07&#730;C) than in the three malaria groups. The mean body temperature of chloroquine treated children with malaria was significantly lower (p Conclusion: The results obtained in this study demonstrate that there was significant positive impact of chloroquine treatment on Plasmodium falciparum parasitemia and degree of anemia in children under 5 years with Plasmodium falciparum in Jos Metropolis.

Structural features of substituted triazole-linked chalcone derivatives as antimalarial activities against D_(10) strains of Plasmodium falciparum: A QSAR approach

A quantitative structure–activity relationship(QSAR) was performed to analyze antimalarial activities against the D10 strains of Plasmodium falciparum of triazole-linked chalcone and dienone hybrid derivatives using partial least squares regression coupled with stepwise forward–backward variable selection method. QSAR analyses were performed on the available IC50 D10 strains of Plasmodium falciparum data based on theoretical molecular descriptors. The QSAR model developed gave good predictive correlation coefficient(r2) of 0.8994, significant cross validated correlation coefficient(q2) of 0.7689, r2 for external test set)(2predr of 0.8256, coefficient of correlation of predicted data set)(2sepred,r of 0.3276. The model shows that antimalarial activity is greatly affected by donor and electron-withdrawing substituents. The study implicates that chalcone and dienone rings should have strong donor and electron-withdrawing substituents as they increase the activity of chalcone. Results show that the predictive ability of the model is satisfactory, and it can be used for designing similar group of antimalarial compounds. The findings derived from this analysis along with other molecular modeling studies will be helpful in designing of the new potent antimalarial activity of clinical utility.

The Relationship between the Plasmodium Falciparum Clearance and the Clinical Effect of the Case with Cerebral Malaria Treated with Artemisinin

Malaria is 1 mosquito-borne disease,which is most commonly caused by a parasite called Plasmodium falciparum(P.falciparum).Cerebral malaria is the most severe neurological complication presented in

Indicators of fatal outcome in severe Plasmodium falciparum malaria:a study in a tertiary-care hospital in Thailand

Objective:To illustrate the clinical features and investigate the indicators associated with a fatal outcome in adult patients with severe Plasmodium falciparum malaria admitted to the Hospital for Tropical Diseases,Bangkok,Thailand.Methods:We studied 202 adult malaria patients admitted to the Intensive Care Unit.A total of 43 clinical variables were identified by univariate and logistic regression analyses,to eliminate confounding factors.Results:Regarding the statistical methods,only 6 variables-jaundice,cerebral malaria,metabolic acidosis,body mass index,initial respiratory rate,and white blood cell count-were significant indicators of death, with adjusted odds ratios(95%CI) of 15.2(2.1-32.3).4.3(2.3-12.6),3.3(2.3-5.7),2.4(1.9-3.5),2.2 (1.5-2.6),and 1.7(1.2-3.1),respectively.Conclusions:Our study found that jaundice,cerebral malaria,metabolic acidosis,body mass index,initial respiratory rate and white blood cell count were indicators of fatal outcome in severe Plasmodium falciparum malaria.Further studies on the fatal indicators in severe malaria need to be compared with data from different geographical areas,to construct practical measures to address potentially fatal indicators in different settings.

Schistosoma haematobium and Plasmodium falciparum coinfection with protection against Plasmodium falciparum malaria in Nigerian children

Objective:Malaria remains the single leading killer of children in sub - Sahara Africa and Schistosomiasis is considered to be second to malaria in global importance.Co - infection of malaria and urinary schistosomiasis has been reported to exacerbate disease morbidity such as anaemia.In different part of the globe,the co - infection between malaria and schistosomiasis provides some protections on the infected persons.The protective effect of this co - infection elucidated immunologically using cytokines is lacking in our locality.Methods:Urine and blood samples obtained from the 160 volunteers were subjected to standard parasitological techniques for diagnosis of urinary schistosomiasis and malaria respectively.Blood samples collected from these volunteers comprising 80 children with schistosomiasis and malaria and the 80 children who had malaria only were subjected to cytokines concentration determination using commercial standard enzyme linked immunosorbent assay kits(Abeam,UK).Results:Eighty participants with co - infection had a mean malarial parasitaemia of 662±201.1μL while the 80 participants with only P.falciparum malaria had a mean malarial parasiteamia of 5943±3270.7μL.Also the volunteers had mean haemoglobin of 11.2 g/dL for co - infected individuals and 5.7 g/dL for participants with single infection of malaria.The serum cytokine levels of the children with S. haematobium and P.falciparum and only P.falciparum infection are as follows;interleukin - 4(16.6 pg/ mL versus 5.2 pg/mL),IL - 5(501.3 pg/mL versus 357.5 pg/mL);IL -8(2 550 pg/mL versus 309 pg/mL),IL - 10(273 pg/mL versus 290 pg/mL),TNF -α(25 pg/mL versus 290 pg/mL) and IFN -γ(21.9 pg/mL versus 2.5 pg/mL).The TNF -α/IL - 10 ratio is 7 for the children with co - infection while those with only P.falciparum malaria infection had a TNF -α/IL - 10 ratio of 0.9.Conclusion:We conclude that the elevated IL - 4,IL - 5,IL - 8 and IFN -γconcentration induced by schistosomiasis altered the Th1/Th 2 profile and protected the children against the morbidity and severity of malaria attack among the children with co - infection.

Higher production of tumor necrosis factor alpha in hemozoin-fed human adherent monocytes is dependent on lipidic component of malarial pigment:new evidences on cytokine regulation in Plasmodium falciparum malaria

Objective:To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment.Methods:Adherent human monocytes were fed for 3 hours with different meals(native hemozoin;lipid free hemozoin;and control latex particles),then tumor necrosis factor alpha was monitored in cell supernatants up to 48 hours through western blotting or specific enzyme-linked immunoadsorbent assay.In selected experiments,unfed monocytes were treated with different doses of 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid or 4-hydroxynonenal instead of phagocytosis.Results:Hemozoin-fed monocytes produced higher levels of tumor necrosis factor alpha than unstimulated and latex-fed cells, while lipid-free hemozoin did not reproduce these results.Additionally,hemozoin effects were mimicked dose-dependently by 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid,but not by 4-hydroxynonenal.Conclusions:Present data suggest an essential role for lipids in hemozoindependent enhanced release of tumor necrosis factor alpha from monocytes,and 15(S,R)hydroxy -6,8,11,13-eicosatetraenoic acid could be one possible specific mediator.

Cortisol and uncomplicated Plasmodium falciparum malaria in an area of unstable malaria transmission in eastern Sudan

Objective:To investigate the levels of serum Cortisol in patients with uncomplicated Plasmodium falciparum(P.falciparum) malaria in an area of unstable malaria transmission in eastern Sudan. Methods:The concentrations of Cortisol were measured in sera of 25 patients with uncomplicated P.fylciparum malaria(at presentation,24 h and 7 d later) and 25 healthy volunteers using radioimmunoassay gamma counter.Results:There was no significant difference in mean(SD) of total Cortisol levels in patients with malaria in comparison with the control group;602.2(369.6) vs. 449.2(311.7) ng/mL,P=0.12.In patients with uncomplicated P.falciparum malaria,the mean(SD) presenting Cortisol levels were significantly higher in comparison to the levels on day 7;602.2 (369.6) vs.373.6(139.1) ng/mL,P=0.009.In the patients with uncomplicated P.falciparum malaria (on presentation) Cortisol levels were not correlated with initial temperature or the presenting parasitaemia.Conclusions:Thus,Cortisol levels were not significantly different between the patients and the controls.

Changing trends in prevalence of different Plasmodium species with dominance of Plasmodium falciparum malaria infection in Aligarh(India)

Objective:To determine the prevalence of malaria in Aligarh and analyze species dominance in different years over a decade.Methods:Diagnosis of malaria was done using microscopy as gold standard,rapid antigen detection assays and quantitative buffy coat(QBC) assays.Giemsa stained blood smear examination was done,thick and thin films were examined for presence of different Plasmodium spp.Rapid antigen detection assays employing detection of HRP-2 and parasite lactate dehydrogenase antigen(pLDH) by immunochromatography was done in patients whose blood smear found to be negative by conventional Giemsa slide examination.QBC was done in cases where there is strong clinical suspicion of malaria with blood smear negative,in patients with chronic malaria,splenomegaly,or in those patients who had inadequate treatment and for post-treatment follow up.Results:Plasmodium vivax and Plasmodium falciparum were only species detected in our hospital.Overall prevalence of malaria in Aligarh was found to be 8.8%.The maximum prevalence of 20.1%was observed in year 2008 and lowest 2.3%in 2002. Conclusions:High prevalence of malaria is observed in this part of country with dominance of both species particularly Plasmodium falciparum should be monitored and factors accounting for occurrence should be studied to employ effective control measures.

Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target

Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum(P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria.

Mapping and Prevalence of Malaria Falciparum Patients with ACT Failed Therapy, in Hanura Public Health Center, Pesawaran, Lampung, Indonesia

Malaria is a public health issue that can cause death. According to the Indonesian Health Profile, in the year 2010, an estimated 45% of Indonesia’s population live in malaria-endemic areas. Pesawaran District is one of the malaria-endemic areas in Lampung province, whose Annual Parasite Incidence in 2010 and 2011 were 2.77 and 4.76 respectively. One of the factors that may inhibit the malaria control is Plasmodium resistance to antimalarial drugs. This study aims to conduct a mapping study and see the prevalence of ACT treatment failure, in Pesawaran District, Lampung Province, Indonesia. Data collection was performed at the Primary Health Centers (PHC) Hanura. A total of 69 samples according to the inclusion and exclusion criteria, the microscopic examination serially for 28 days was done. Microscopic examination performed on D0, D1, D2, D3, D7, D14, D28, and a complaint is found outside the schedule. Coordinates of patient house, determined using GPS. Based on observations, microscopic examination and spatial analysis, the prevalence of ACT treatment failure in patients with falcipaum malaria was 11.59%. The malaria falcifarum patient spread around the coast, that were near vector breeding places. There were five clusters of malaria falciparum patients and one cluster of malaria falciparum patient with treatment failure that were formed. Only one significant cluster of malaria falciparum patient (P = 0.0027, radius 0 km) is found, while the other cluster is not statistically significant. The cluster of malaria falciparum patient with treatment failure was not statistically significant (P = 1.000, radius 0.15 km), but this cluster is located in the area of the suspected vector breeding place. The cluster formation means that people living within a radius of these clusters have a greater risk to get malaria infection.